Kanji Ogata

α2-PLASMIN-INHIBITOR DEFICIENCY (MIYASATO DISEASE)

A 25-year-old man, born in Okinawa, Japan, had a haemorrhagic diathesis characterised by prolonged bleeding and ecchymoses after minor trauma and spontaneous joint haemorrhage. The frequency and severity of these episodes were reduced by an antiplasminic drug. Routine coagulation studies revealed no abnormalities except for significantly sshortened euglobulin-lysis time and whole-blood clot lysis time. Activities of all known clotting and fibrinolytic factors were within normal ranges but no circulating alpha2-plasmin inhibitor was found in the plasma. alpha2-plasmin inhibitor is a potent and fast-acting protease inhibitor. Studies of family members indicated that this abnormality was inherited as an autosomal and recessive gene.

Heterogeneity of factor IX BM difference of cleavage sites by factor XIa and Ca2+in factor IX Kashihara, Factor IX Nagoya and Factor IX Niigata

Abnormal factor IX was isolated from the plasma of a patient with hemophilia B Kashihara and two patients with hemophilia BM. The F.IX was purified to homogeneity by using monoclonal anti-F.IX-Sephrose, heparin-Sepharose and DEAE-Sephadex A-50 affinity chromatography successively. The isolated proteins have the same molecular weight and the same mobility on crossed immunoelectrophoresis as normal F.IX. The limited proteolysis of purified proteins was induced by F.XIa/Ca2+ or by RVV-X/Ca2+. A time course study showed that F.IX Nagoya seemed to be cleaved by neither F.XIa nor RVV-X, F.IX Kashihara was cleaved partially by F.XIa but not by RVV-X, and that F.IX Niigata was cleaved completely at the rate similar to normal F.IX, though the resultant product of F.IX Niigata did not show any F.IXa activity. These results favored the view that hemophilia B+ or BM is a heterogeneous disorder.

Sensitive Solid Phase Enzyme Immunoassay for Factor IX Antigen and Classification of Hemophilia B

A sensitive solid phase enzyme immunoassay (EIA) was developed for the measurement of factor IX antigen (IX:AG), using rabbit antihuman factor IX antiserum and beta-D-galactosidase, which enabled us to detect IX:AG as low as 10(-4)U/ml. 37 patients with severe hemophilia B have been investigated by EIA, inhibitor neutralization assay and bovine brain prothrombin time. They could be divided into four genetic variants. 25% had normal levels of IX:AG but decreased levels of factor IX clotting activity. On crossed immunoelectrophoresis of the hemophilia B+ and hemophilia BM, we could not find abnormalities in electrophoretic mobilities compared to normal subjects in the presence of 1 mM Ca++ lactate.